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The Dyspepsia Educational Tool As a Novel Aid in Dyspepsia Management
Published on: June 29, 2019
The associations between functional dyspepsia and potential risk factors: A comprehensive Mendelian randomization
Zeyu Wang1, Tangyi Liu1, Dan Cao1
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China.
Background:
Previous cross-sectional studies have identified multiple potential risk factors for functional dyspepsia (FD). However, the causal associations between these factors and FD remain elusive. Here we aimed to fully examine the causal relationships between these factors and FD utilizing a two-sample MR framework.
Methods:
A total of 53 potential FD-related modifiable factors, including those associated with hormones, metabolism, disease, medication, sociology, psychology, lifestyle and others were obtained through a comprehensive literature review. Independent genetic variants closely linked to these factors were screened as instrumental variables from genome-wide association studies (GWASs). A total of 8875 FD cases and 320387 controls were available for the analysis. The inverse variance weighted (IVW) method was employed as the primary analytical approach to assess the relationship between genetic variants of risk factors and the FD risk. Sensitivity analyses were performed to evaluate the consistency of the findings using the weighted median model, MR-Egger and MR-PRESSO methods.
Results:
Genetically predicted depression (OR 1.515, 95% confidence interval (CI) 1.231 to 1.865, p = 0.000088), gastroesophageal reflux disease (OR 1.320, 95%CI 1.153 to 1.511, p = 0.000057) and years of education (OR 0.926, 95%CI 0.894 to 0.958, p = 0.00001) were associated with risk for FD in univariate MR analyses. Multiple medications, alcohol consumption, poultry intake, bipolar disorder, mood swings, type 1 diabetes, elevated systolic blood pressure and lower overall health rating showed to be suggestive risk factors for FD (all p<0.05 while ≥0.00167). The positive causal relationship between depression, years of education and FD was still significant in multivariate MR analyses.
Conclusions:
Our comprehensive MR study demonstrated that depression and lower educational attainment were causal factors for FD at the genetic level.
Insights
This study used MR to investigate causal links between risk factors and functional dyspepsia (FD). Results show depression and lower education are genetic causes of FD, highlighting their importance in disease prevention.
Area of Science:
- Gastroenterology
- Genetics
- Epidemiology
Background:
- Functional dyspepsia (FD) has many suspected risk factors, but causal links are unclear.
- Previous studies were cross-sectional, limiting causal inference.
- This study uses a robust MR framework to explore causality.
Purpose of the Study:
- To investigate the causal relationships between 53 potential risk factors and functional dyspepsia (FD).
- To leverage genetic variants as instrumental variables for a Mendelian randomization (MR) analysis.
- To identify genetically determined causal factors for FD.
Main Methods:
- A comprehensive literature review identified 53 potential modifiable risk factors for FD.
- Genome-wide association study (GWAS) data were used to select genetic variants as instrumental variables.
- Two-sample Mendelian randomization (MR) analysis with inverse variance weighted (IVW) as the primary method was employed.
Main Results:
- Genetically predicted depression (OR 1.515) and gastroesophageal reflux disease (OR 1.320) were significantly associated with increased FD risk.
- Lower years of education (OR 0.926) showed a significant association with decreased FD risk.
- Multivariate MR confirmed depression and lower educational attainment as significant causal factors for FD.
Conclusions:
- Depression and lower educational attainment are identified as causal factors for functional dyspepsia (FD) at the genetic level.
- These findings underscore the importance of addressing mental health and socioeconomic factors in FD prevention and management.
- The study provides strong evidence for genetic causality, moving beyond correlational observations.
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